The adipokine chemerin augments vascular reactivity to contractile stimuli via activation of the MEK-ERK1/2 pathway

Lobato, N. S. and Neves, K. B. and Filgueira, F. P. and Fortes, Z. B. and Carvalho, M. H. C. and Webb, R. C. and Oliveira, A. M. and Tostes, R. C. (2012) The adipokine chemerin augments vascular reactivity to contractile stimuli via activation of the MEK-ERK1/2 pathway. Life Sciences, 91 (13-14). pp. 600-606. ISSN 0024-3205 (https://doi.org/10.1016/j.lfs.2012.04.013)

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Abstract

Aims Cytokines interfere with signaling pathways and mediators of vascular contraction. Endothelin-1 (ET-1) plays a major role on vascular dysfunction in conditions characterized by increased circulating levels of adipokines. In the present study we tested the hypothesis that the adipokine chemerin increases vascular contractile responses via activation of ET-1/ET-1 receptors-mediated pathways. Main methods Male, 10–12 week-old Wistar rats were used. Endothelium-intact and endothelium-denuded aortic rings were incubated with chemerin (0.5 ng/mL or 5 ng/mL, for 1 or 24 h), and isometric contraction was recorded. Protein expression was determined by Western blotting. Key findings Constrictor responses to phenylephrine (PE) and ET-1 were increased in vessels treated for 1 h with chemerin. Chemerin incubation for 24 h decreased PE contractile response whereas it increased the sensitivity to ET-1. Endothelium removal significantly potentiated chemerin effects on vascular contractile responses to PE and ET-1. Incubation with either an ERK1/2 inhibitor (PD98059) or ETA antagonist (BQ123) abolished chemerin effects on PE- and ET-1-induced vasoconstriction. Phosphorylation of MEK1/2 and ERK1/2 was significantly increased in vessels treated with chemerin for 1 and 24 h. Phosphorylation of these proteins was further increased in vessels incubated with ET-1 plus chemerin. ET-1 increased MEK1/2, ERK1/2 and MKP1 protein expression to values observed in vessels treated with chemerin. Significance Chemerin increases contractile responses to PE and ET-1 via ERK1/2 activation. Our study contributes to a better understanding of the mechanisms by which the adipose tissue affects vascular function and, consequently, the vascular alterations present in obesity and related diseases.

ORCID iDs

Lobato, N. S., Neves, K. B. ORCID logoORCID: https://orcid.org/0000-0001-5158-9263, Filgueira, F. P., Fortes, Z. B., Carvalho, M. H. C., Webb, R. C., Oliveira, A. M. and Tostes, R. C.;
  • Item type:Article
    ID code:82754
    Dates:
    Date
    Event
    15 October 2012
    Published
    3 April 2012
    Accepted
    Notes:The adipokine chemerin augments vascular reactivity to contractile stimuli via activation of the MEK-ERK1/2 pathway, Life Sciences, Volume 91, Issues 13–14, 2012, https://doi.org/10.1016/j.lfs.2012.04.013
    Subjects:Medicine
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Faculty of Science > Physics
    Depositing user: Pure Administrator
    Date deposited:13 Oct 2022 13:15
    Last modified:11 Nov 2024 13:39
    URI:https://strathprints.strath.ac.uk/id/eprint/82754
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